This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. The polypeptide of the present invention has been putatively identified as a cytokine, more particularly, the polypeptide of the present invention has been identified as an immune cell cytokine-like potential hormone, sometimes hereinafter referred to as xe2x80x9cHLHDC84xe2x80x9d. The invention also relates to inhibiting the action of such polypeptides.
The cytokine family of proteins exhibit a wide variety of functions. A hallmark feature is their ability to elicit chemotactic migration of distinct cell types, including polymorphonuclear cells and macrophages. Many cytokines have pro-inflammatory activity and are involved in multiple steps during inflammatory reactions. In addition to their involvement in inflammation, cytokines have been shown to exhibit other activities. For example, interleukin-8 (IL-8) promotes proliferation of keratinocytes.
In light of the diverse biological activities, it is not surprising that cytokines have been implicated in a number of physiological and disease conditions, including lymphocyte trafficking, wound healing, hematopoietic regulation and immunological disorders such as allergy, asthma and arthritis.
The protein of the present invention is a secreted protein, similar to cytokine proteins, and is most homologous at the amino acid level to the fringe (fng) gene of Drosophila.
The fringe (fng) gene, encodes a molecule that mediates signaling between distinct cell populations (Irvine, K. D. and Wieschaus, E., Cell, 79:595-506 (1994). The fng gene encodes a putatively secreted protein, and mediates processes that establish the wing margin and promote wing outgrowth without otherwise affecting dorsal-ventral wing cell identity.
The fng cDNA includes a 412 codon open reading frame encoding for a novel protein. Notably, this predicted protein product includes a signal sequence at its amino-terminal end but lacks predicted transmembrane domains, suggesting that it is secreted (Kyte J. and Doolittle, R. F., J. Mol. Biol., 157:105-132 (1982); Eisenberg, D., et al., J. Mol. Biol., 179:125-142 (1984); von Heijne, G., Nucl. Acids Res. 14:4583-4690 (1986)). fng may have a role in cell-cell interactions promoting wing margin formation and wing growth. The fng gene affects a class of epithelial cells which ultimately form the wing. This is done by altering the differentiation state of the cells and enhancing their proliferation.
In accordance with one aspect of the present invention, there are provided novel polypeptides as well as biologically active and diagnostically or therapeutically useful fragments, analogs and derivatives thereof.
In accordance with another aspect of the present invention, there are provided isolated nucleic acid molecules encoding such polypeptides, including mRNAs, cDNAs, genomic DNA as well as biologically active and diagnostically or therapeutically useful fragments, analogs and derivatives thereof.
In accordance with another aspect of the present invention there is provided an isolated nucleic acid molecule encoding a mature polypeptide expressed by the DNA contained in ATCC Deposit No. 97351.
In accordance with another aspect of the present invention there are provided nucleic acid probes comprising nucleic acid molecules of sufficient length to specifically hybridize to sequences of the present invention.
In accordance with yet a further aspect of the present invention, there is provided a process for producing such polypeptides by recombinant techniques which comprises culturing recombinant prokaryotic and/or eukaryotic host cells, containing a nucleic acid sequence of the present invention, under conditions promoting expression of said protein and subsequent recovery of said protein.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptides, or polynucleotides encoding such polypeptides for therapeutic purposes, for example, to stimulate the proliferation, mobilization and differentiation of stem cells in the immune system for autologous transplant and for treating auto-immune disorders, to stimulate growth factor activity and neuronal re-growth and to treat inflammatory disorders.
In accordance with yet a further aspect of the present invention, there are provided antibodies against such polypeptides and a method of employing such antibodies to limit cellular proliferation or induced differentiation of stem cells for the purpose of treating and/or preventing leukemia and lymphoblastoma and as a diagnostic to detect cancer.
In accordance with yet another aspect of the present invention, there are provided antagonists to such polypeptides, which may be used to inhibit the action of such polypeptides, for example, in the treatment of leukemia or lymphoblastoma, arthritis and as adjunct treatment during chemotherapy.
In accordance with another aspect of the present invention there is provided a method of diagnosing a disease or a susceptibility to a disease related to a mutation in the nucleic acid sequences and the protein encoded by such nucleic acid sequences.
In accordance with another aspect of the present invention there is provided a method of delivering the polynucleotide of the present invention to cells of a patient, either ex vivo or in vivo, such that the gene product of the present invention is administered to the patient.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptides, or polynucleotides encoding such polypeptides, for in vitro purposes related to scientific research, synthesis of DNA and manufacture of DNA vectors.
These and other aspects of the present invention should be apparent to those skilled in the art from the teachings herein.
The following drawings are illustrative of embodiments of the invention and are not meant to limit the scope of the invention as encompassed by the claims.